GSK's Novel TB Vaccine Shows Breakthrough Efficacy; AstraZeneca's PD-L1 Inhibitor Poised to Enter First-Line Lung Cancer Therapy

“Drawing the Sword” Against Inflammatory Bowel Disease! Zealand Pharma Spends $80 Million to Acquire Macrocyclic Peptide Platform

Zealand Pharma, a Danish biopharmaceutical company focused on peptide drug development, has announced that it will acquire Toronto-based biotechnology company Encycle Therapeutics for $80 million. Encycle possesses an advanced biotechnology platform capable of rapidly synthesizing novel macrocyclic peptides. The acquisition aims to strengthen Zealand’s peptide drug development and its leadership position in the treatment of gastrointestinal diseases.

Encycle’s leading drug candidate, ET3764, is an oral inhibitor targeting integrin α4β7. Integrin α4β7 is a key therapeutic target for inflammatory bowel disease (IBD). It is expressed on the surface of certain circulating leukocytes and serves as a core adhesion molecule that mediates the migration of pro-inflammatory lymphocytes to gut-associated lymphoid tissues. ET3764 binds to the binding site of integrin α4β7, thereby potentially inhibiting its interaction with mucosal addressin cell adhesion molecule-1 (MAdCAM-1) and consequently limiting the ability of these pro-inflammatory lymphocytes to infiltrate intestinal tissues. Vedolizumab, which shares a similar therapeutic target, has been approved in multiple countries for the treatment of ulcerative colitis and Crohn’s disease.

▲Encycle’s leading drug candidate ET3764 (Image source: SEC)

This collaboration will also grant Zealand access to a screening library of more than 5,000 macrocyclic peptides. These macrocyclic peptides exhibit physicochemical properties such as high tissue permeability and oral bioavailability, holding potential for development into next-generation therapeutics.

Good News for Lung Cancer Patients! AstraZeneca’s PD-L1 Inhibitor Combination Therapy Meets Phase 3 Endpoints

AstraZeneca announced that its combination therapy consisting of the PD-L1 monoclonal antibody Imfinzi (durvalumab) and chemotherapy, as well as the triplet regimen with the addition of the anti-CTLA-4 antibody tremelimumab, met the primary and key secondary endpoints in the Phase 3 POSEIDON clinical trial for first-line treatment of patients with stage IV non-small cell lung cancer (NSCLC). Compared with chemotherapy alone, both combination regimens demonstrated statistically significant and clinically meaningful improvements in progression-free survival (PFS).

Imfinzi is a humanized PD-L1 monoclonal antibody that binds to PD-L1 and blocks its interaction with the PD-1 and CD80 receptors, thereby inhibiting the suppressive effect of PD-L1 on the immune response. Imfinzi has received FDA approval for the treatment of patients with previously treated advanced bladder cancer and patients with previously treated, unresectable stage III non-small cell lung cancer (NSCLC).

The POSEIDON trial is a randomized, international, multicenter Phase 3 clinical study. The patient population included individuals with metastatic non-small cell lung cancer (NSCLC), both squamous and non-squamous histologies, who expressed PD-L1 and did not harbor EGFR or ALK gene mutations. The primary endpoints of the trial were progression-free survival (PFS) and overall survival (OS) in NSCLC patients treated with Imfinzi in combination with chemotherapy. Key secondary endpoints included PFS and OS in patients receiving the triplet regimen of Imfinzi plus tremelimumab and chemotherapy. The results demonstrated that, compared with chemotherapy alone, both the Imfinzi-chemotherapy doublet and the tremelimumab-containing triplet therapy significantly improved PFS, thereby meeting the primary and key secondary endpoints of the study. Detailed data from this trial will be presented at future medical conferences.

A Breakthrough in Nearly a Century! GSK’s Tuberculosis Vaccine Shows Positive Results in Phase 2b Trial

GlaxoSmithKline (GSK) and the International AIDS Vaccine Initiative (IAVI) jointly announced that GSK’s investigational vaccine M72/AS01E significantly reduced the incidence of tuberculosis (TB) among HIV-negative adults with latent TB infection in a Phase 2b clinical trial, demonstrating 50% vaccine efficacy within three years post-vaccination. The results of this trial have been published in the New England Journal of Medicine (NEJM).

GSK’s candidate vaccine, M72/AS01E, contains the M72 recombinant protein derived from two Mycobacterium tuberculosis antigens (Mtb32A and Mtb39A), along with the AS01 adjuvant system. This adjuvant system has already been used in GSK’s malaria and shingles vaccines. The vaccine can stimulate specific lymphocyte proliferation and/or interferon-gamma production, thereby playing a role in preventing pulmonary tuberculosis.

In this randomized, double-blind, placebo-controlled Phase 2b clinical trial, 3,573 HIV-negative adults with latent tuberculosis infection were randomly assigned to two groups to receive either the M72/AS01E vaccine or a placebo, and were followed for three years to monitor for the development of active tuberculosis. The results showed that 13 cases of tuberculosis occurred in the vaccine group, compared with 26 cases in the placebo group, indicating a vaccine efficacy of 50% for M72/AS01E.

“Superbugs” Beware! GSK Initiates Phase 3 Clinical Trial for Antibiotic with Novel Mechanism of Action

GlaxoSmithKline (GSK) announced that the first patient has been dosed in its Phase 3 trials of gepotidacin, an investigational triazaacenaphthylene antibiotic with a novel mechanism of action, for the treatment of uncomplicated urinary tract infections (uUTI, also known as acute cystitis) and urogenital gonorrhea (GC).

Gepotidacin is orally available and features a dual mechanism of action, selectively binding to and inhibiting both DNA gyrase and DNA topoisomerase IV, thereby inducing single-strand breaks in replicating DNA and ultimately achieving pathogen eradication.

▲Molecular structure of gepotidacin and schematic diagram of its dual mechanism of action (Image source: Biorxiv.org)

Gepotidacin is the result of a collaboration between GSK, the U.S. Biomedical Advanced Research and Development Authority (BARDA), and the Defense Threat Reduction Agency (DTRA). Previously, gepotidacin demonstrated favorable efficacy in two Phase 2 trials targeting gonococcal infections (GC) and acute bacterial skin and skin structure infections (ABSSSI). In adult patients with uncomplicated GC, gepotidacin achieved a 95% cure rate against Neisseria gonorrhoea.

GSK will conduct the EAGLE-1 trial evaluating gepotidacin as a first-line therapy for gonorrhea (GC), and the EAGLE-2 trial comparing the efficacy and safety of gepotidacin with ceftriaxone plus azithromycin for the treatment of uncomplicated urinary tract infections (uUTI).

Significant Reduction in Relapse Risk! FDA/EMA Accepts Roche’s Marketing Application for IL-6 Receptor Antibody

Genentech, a member of the Roche Group, announced that the U.S. Food and Drug Administration (FDA) has accepted its Biologics License Application (BLA) for satralizumab, an interleukin-6 (IL-6) receptor antibody, for the treatment of adult and adolescent patients with neuromyelitis optica spectrum disorder (NMOSD). Meanwhile, the European Medicines Agency (EMA) has also accepted the Marketing Authorization Application (MAA) for satralizumab and granted it Accelerated Assessment status. The FDA and the EMA’s Committee for Medicinal Products for Human Use (CHMP) are expected to issue decisions on these applications in 2020.

▲Introduction to Satralizumab (Image source: Roche official website)

This application is based on the positive results from two pivotal Phase 3 clinical studies, named SakuraStar and SAkuraSky. These trials evaluated the efficacy and safety of satralizumab as monotherapy and in combination with standard therapy, respectively, in patients with neuromyelitis optica spectrum disorder (NMOSD). The results of the SakuraStar study showed that, compared with the placebo group, patients receiving satralizumab monotherapy had a 55% reduction in the risk of relapse. The relapse-free rates at 96 weeks and 48 weeks were 76.1% and 72.1%, respectively, whereas these rates in the placebo group were 61.9% and 51.2%. Furthermore, in the subgroup of patients positive for aquaporin-4 (AQP4) autoantibodies, those treated with satralizumab monotherapy experienced a 74% reduction in relapse risk. The relapse-free rates at 96 weeks and 48 weeks were 76.5% and 82.9%, respectively, compared to 41.1% and 55.4% in the placebo group.

The SAkuraSky study results showed that, compared with the placebo group, patients receiving satralizumab in combination with standard therapy had a 62% reduction in the risk of relapse. The relapse-free rates at 96 weeks and 48 weeks were 77.6% and 88.9%, respectively, whereas these rates in the placebo group were 58.7% and 66%, respectively. In the subgroup of patients positive for AQP4 autoantibodies, those receiving satralizumab in combination with standard therapy had a 79% reduction in the risk of relapse. The relapse-free rates at 96 weeks and 48 weeks were 91.5%, whereas these rates in the placebo group were 53.3% and 59.9%, respectively.

Targeting All “Major KRAS Mutants”! Pan-KRAS Inhibitors Advance into Clinical Trials

At the 31st AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, Boehringer Ingelheim presented positive preclinical data for BI 1701963, its first pan-KRAS inhibitor targeting all major KRAS mutants, and announced the advancement of this investigational drug into clinical development. The drug will be evaluated as a monotherapy or in combination with the MEK inhibitor trametinib for the treatment of patients with various types of advanced solid tumors. This pan-KRAS inhibitor has the potential to block the activity of KRAS mutants in 15% of cancers.

▲ Schematic diagram of the mechanism of action of SOS1 inhibitors (Image source: Boehringer Ingelheim official website)

BI 1701963 is an oral, specific SOS1 inhibitor that suppresses KRAS activity by binding to the SOS1 protein. Preclinical data indicate that pan-KRAS inhibitors can inhibit the activity of KRAS G12 and KRAS G13 mutants, thereby slowing tumor growth. In non-clinical studies, BI 1701963 demonstrated a significant impact on KRAS signaling when combined with a MEK inhibitor, enhancing antitumor activity through complementary mechanisms of action. Recently, Boehringer Ingelheim entered into a research and development agreement with Lupin Pharmaceuticals to explore the efficacy of combination therapy comprising a KRAS inhibitor and Lupin’s novel MEK inhibitor, LNP3794, in clinical trials.

“Targeting” Toxic Tau Protein! Innovative Therapy for Neurodegenerative Diseases Enters Clinical Trials

Pinteon Therapeutics Announces Clinical Development of PNT001, a Novel Antibody Targeting the Neurotoxic cis-pT231-tau Conformation, for the Treatment of Neurodegenerative Diseases Including Alzheimer’s Disease (AD), Progressive Supranuclear Palsy (PSP), and Moderate Traumatic Brain Injury (TBI)

Tau protein is a protein closely associated with neurodegenerative diseases such as Alzheimer’s disease (AD) in brain tissue. Normal tau protein maintains the stability of the microtubule system and facilitates the transport of proteins and nucleotides within neuronal cells. However, abnormal folding of tau protein results in conformations with high neurotoxicity. The cis-p-tau conformation of tau promotes its abnormal aggregation in neurons, leading to the formation of tau tangles. These neurofibrillary tangles are a hallmark pathological feature of many neurodegenerative diseases and are associated with neuronal death, brain atrophy, and memory loss.

▲Targeting the cis-pT231-tau neurotoxic epitope to prevent the spread of toxic tau protein (Image source: Pinteon official website)

Currently, most tau antibodies in development target both normal and pathological tau proteins. In contrast, Pinteon’s lead candidate, PNT001, is the only novel tau antibody that specifically targets the cis-pT231-tau conformation. Cis-pT231-tau is a neurotoxic conformation that has been confirmed in preclinical studies to be one of the primary drivers of neurodegenerative diseases. By precisely targeting and neutralizing tau proteins bearing the cis-pT231 epitope, PNT001 blocks the spread of toxic tau, thereby preserving normal brain function and treating neurodegenerative diseases.

$2.1 Billion! Google Acquires Wearable Health Device Developer Fitbit

Google Announces Acquisition of Fitbit, a Developer of Wearable Health Devices, to Gain Its Fitness Trackers and Proprietary Health Records Platform, Further Advancing Google’s New Products in the Healthcare Sector. Reportedly, This Marks Google’s Second Wearable Device Acquisition This Year. In January, Google Spent $40 Million to Acquire Smartwatch Technology Developed by Fossil.

Image source: Fitbit official website

Fitbit’s fitness trackers incorporate an intelligent sensor system that continuously monitors personal health metrics around the clock, including heart rate, calorie expenditure, and sleep patterns. They also cater to daily needs such as notifications, phone calls, and payments. Featuring a novel, lightweight, and wearable design, these devices help users achieve fitness goals and adopt healthier lifestyles, thereby improving overall health.

Under the terms of the agreement, Fitbit will continue to work with Android and Apple’s iOS to ensure the normal operation of its health records platform. Additionally, Fitbit had previously partnered with Bristol-Myers Squibb (BMS) and Pfizer to help these companies develop wearable atrial fibrillation monitors, and this acquisition has also established new connections between Google and these two companies.

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